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溶瘤病毒疗法改善了针对胶质母细胞瘤肿瘤干性的免疫疗法。

Oncolytic virotherapy improves immunotherapies targeting cancer stemness in glioblastoma.

机构信息

Department of Medical Virology, The Persian Gulf Tropical Medicine Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran.

Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan 8174673461, Iran; Pediatric Inherited Diseases Research Center, Isfahan University of Medical Sciences, Isfahan 8174673461, Iran.

出版信息

Biochim Biophys Acta Gen Subj. 2024 Sep;1868(9):130662. doi: 10.1016/j.bbagen.2024.130662. Epub 2024 Jun 18.

Abstract

Despite advances in cancer therapies, glioblastoma (GBM) remains the most resistant and recurrent tumor in the central nervous system. GBM tumor microenvironment (TME) is a highly dynamic landscape consistent with alteration in tumor infiltration cells, playing a critical role in tumor progression and invasion. In addition, glioma stem cells (GSCs) with self-renewal capability promote tumor recurrence and induce therapy resistance, which all have complicated eradication of GBM with existing therapies. Oncolytic virotherapy is a promising field of therapy that can kill tumor cells in a targeted manner. Manipulated oncolytic viruses (OVs) improve cancer immunotherapy by directly lysis tumor cells, infiltrating antitumor cells, inducing immunogenic cell death, and sensitizing immune-resistant TME to an immune-responsive hot state. Importantly, OVs can target stemness-driven GBM progression. In this review, we will discuss how OVs as a therapeutic option target GBM, especially the GSC subpopulation, and induce immunogenicity to remodel the TME, which subsequently enhances immunotherapies' efficiency.

摘要

尽管癌症治疗取得了进展,但胶质母细胞瘤(GBM)仍然是中枢神经系统中最具耐药性和复发性的肿瘤。GBM 肿瘤微环境(TME)是一个高度动态的景观,与肿瘤浸润细胞的改变一致,在肿瘤进展和侵袭中发挥关键作用。此外,具有自我更新能力的神经胶质瘤干细胞(GSCs)促进肿瘤复发并诱导治疗耐药性,这使得现有的治疗方法难以彻底清除 GBM。溶瘤病毒治疗是一种很有前途的治疗方法,可以靶向杀死肿瘤细胞。经过改造的溶瘤病毒(OVs)通过直接溶解肿瘤细胞、浸润抗肿瘤细胞、诱导免疫原性细胞死亡以及使免疫抵抗的 TME 敏感化为免疫应答的热状态,改善癌症免疫疗法。重要的是,OVs 可以针对以干性为驱动的 GBM 进展。在这篇综述中,我们将讨论 OVs 如何作为一种治疗选择靶向 GBM,特别是 GSC 亚群,并诱导免疫原性以重塑 TME,从而提高免疫疗法的效率。

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